An effective, non-invasive oral delivery system for peptides, in general, and insulin, in particular, has not been developed to date, due to several limiting factors. First, tablets or liquids containing peptides, such as insulin, are readily digested in the harsh stomach environment, and thus require extensive protection to survive and be absorbed. Food effects and individual gastrointestinal (GI) transit times confound a dependable temporal or quantitative delivery.
The lack of effective oral delivery means is further complicated in some cases. For example, insulin is most stable in its hexameric form (six insulin monomers assembled around zinc ions). Therefore, it is preferable to store it in this form for greater shelf-life stability. However, this form is too large for rapid absorption though tissue membranes.
U.S. Pat. No. 6,676,931 to Dugger, III discloses liquid sprays that deliver an active agent to the mouth for absorption through the oral mucosa. U.S. Pat. No. 6,676,931 notes that the active agent may be insulin lispro, which is a rapidly-acting human insulin analog that contains hexameric insulin. However, such liquid sprays are not very useful for delivering hexameric insulin due to its poor absorption. Additionally, many active agents are not stable in the liquid form and cannot be stored in liquid form.
Buccal administration using sprays of insulin has been attempted with limited bioavailability since hexameric insulin is not readily absorbed and liquids are eventually swallowed. The administered dose is not rapidly absorbed, and has an absorption profile similar to subcutaneous injection. Also, due to its poor bioavailability, a large dose is required for a useful glucose lowering effect. Thus, it is not a cost effective or therapeutic alternative.
Pulmonary formulations are being developed and may provide a good alternative to injection. However, these formulations require the use of an inhaler and may lack good patient compliance if the delivery technique is complicated.
Therefore it is an object of the invention to provide oral drug delivery compositions with improved stability and rapid onset of action.
It is a further object of the invention to provide methods for storing drugs and rapidly delivering drugs.